Transplantation of autologous skin grafts and tissue engineered skin replacements for the treatment of burns, trauma, and ulcerative wounds has been shown to restore a protective barrier to infection and fluid loss, reduce beat loss, provide mechanical strength, diminish pain, and dampen the hypermetabolic stress response to thermal injury. Patencies of these grafts depend mainly on the high viability and sustained function of the enmeshed keratinocytes. With growing demand in tissue replacement therapies, development of successful and economical preservation techniques for skin grafts and replacements becomes essential. In this regard, if attained, desiccated state storage offers an economical solution to availability, storage, and transportation problems. Recent studies indicate that carbohydrates are very efficient in stabilizing mammalian cells against various types of stresses, including those associated with cryopreservation and desiccation. In this study we introduce the use of 3-O-methyl-D-glucose (3-OMG), a nonmetabolizable glucose derivative, as a new means of providing protection for keratinocytes undergoing desiccation. We show that with decreasing water contents, viability of the cells decreases; however, at the same water content the immediate post-rehydration viability and long-term survival of the cells exposed to 3-OMG are much higher than those of controls.